Margination of fluorescent polylactic acid-polyaspartamide based nanoparticles in microcapillaries in vitro: The effect of hematocrit and pressure

Gaetano Giammona, Gennara Cavallaro, Emanuela Fabiola Craparo, Gaetano Giammona, Rosa D'Apolito

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Abstract

The last decade has seen the emergence of vascular-targeted drug delivery systems as a promising approach for the treatment of many diseases, such as cardiovascular diseases and cancer. In this field, one of the major challenges is carrier margination propensity (i.e., particle migration from blood flow to vessel walls); indeed, binding of these particles to targeted cells and tissues is only possible if there is direct carrier-wall interaction. Here, a microfluidic system mimicking the hydrodynamic conditions of human microcirculation in vitro is used to investigate the effect of red blood cells (RBCs) on a carrier margination in relation to RBC concentration (hematocrit) and pressure drop. As model drug carriers, fluorescent polymeric nanoparticles (FNPs) were chosen, which were obtained by using as starting material a pegylated polylactic acid-polyaspartamide copolymer. The latter was synthesized by derivatization of,-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) with Rhodamine (RhB), polylactic acid (PLA) and then poly(ethyleneglycol) (PEG) chains. It was found that the carrier concentration near the wall increases with increasing pressure drop, independently of RBC concentration, and that the tendency for FNP margination decreases with increasing hematocrit. This work highlights the importance of taking into account RBC-drug carrier interactions and physiological conditions in microcirculation when planning a drug delivery strategy based on systemically administered carriers.
Lingua originaleEnglish
pagine (da-a)1845-
Numero di pagine12
RivistaMolecules
Volume22
Stato di pubblicazionePublished - 2017

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hematocrit
Hematocrit
Nanoparticles
Blood
Erythrocytes
Pressure
nanoparticles
erythrocytes
acids
Drug Carriers
Microcirculation
drugs
Pressure drop
Rhodamines
Microfluidics
pressure drop
Hydrodynamics
Drug Delivery Systems
Drug Interactions
delivery

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Organic Chemistry
  • Physical and Theoretical Chemistry
  • Drug Discovery
  • Pharmaceutical Science
  • Molecular Medicine
  • Chemistry (miscellaneous)

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title = "Margination of fluorescent polylactic acid-polyaspartamide based nanoparticles in microcapillaries in vitro: The effect of hematocrit and pressure",
abstract = "The last decade has seen the emergence of vascular-targeted drug delivery systems as a promising approach for the treatment of many diseases, such as cardiovascular diseases and cancer. In this field, one of the major challenges is carrier margination propensity (i.e., particle migration from blood flow to vessel walls); indeed, binding of these particles to targeted cells and tissues is only possible if there is direct carrier-wall interaction. Here, a microfluidic system mimicking the hydrodynamic conditions of human microcirculation in vitro is used to investigate the effect of red blood cells (RBCs) on a carrier margination in relation to RBC concentration (hematocrit) and pressure drop. As model drug carriers, fluorescent polymeric nanoparticles (FNPs) were chosen, which were obtained by using as starting material a pegylated polylactic acid-polyaspartamide copolymer. The latter was synthesized by derivatization of,-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) with Rhodamine (RhB), polylactic acid (PLA) and then poly(ethyleneglycol) (PEG) chains. It was found that the carrier concentration near the wall increases with increasing pressure drop, independently of RBC concentration, and that the tendency for FNP margination decreases with increasing hematocrit. This work highlights the importance of taking into account RBC-drug carrier interactions and physiological conditions in microcirculation when planning a drug delivery strategy based on systemically administered carriers.",
keywords = "Margination; Poly(ethylene glycol) (PEG); Poly(lactic acid) (PLA); Polymeric nanoparticles; alpha,beta-poly-(N-2-hydroxyethyl)-DL-aspartamide (PHEA);",
author = "Gaetano Giammona and Gennara Cavallaro and Craparo, {Emanuela Fabiola} and Gaetano Giammona and Rosa D'Apolito",
year = "2017",
language = "English",
volume = "22",
pages = "1845--",
journal = "Molecules",
issn = "1420-3049",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

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TY - JOUR

T1 - Margination of fluorescent polylactic acid-polyaspartamide based nanoparticles in microcapillaries in vitro: The effect of hematocrit and pressure

AU - Giammona, Gaetano

AU - Cavallaro, Gennara

AU - Craparo, Emanuela Fabiola

AU - Giammona, Gaetano

AU - D'Apolito, Rosa

PY - 2017

Y1 - 2017

N2 - The last decade has seen the emergence of vascular-targeted drug delivery systems as a promising approach for the treatment of many diseases, such as cardiovascular diseases and cancer. In this field, one of the major challenges is carrier margination propensity (i.e., particle migration from blood flow to vessel walls); indeed, binding of these particles to targeted cells and tissues is only possible if there is direct carrier-wall interaction. Here, a microfluidic system mimicking the hydrodynamic conditions of human microcirculation in vitro is used to investigate the effect of red blood cells (RBCs) on a carrier margination in relation to RBC concentration (hematocrit) and pressure drop. As model drug carriers, fluorescent polymeric nanoparticles (FNPs) were chosen, which were obtained by using as starting material a pegylated polylactic acid-polyaspartamide copolymer. The latter was synthesized by derivatization of,-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) with Rhodamine (RhB), polylactic acid (PLA) and then poly(ethyleneglycol) (PEG) chains. It was found that the carrier concentration near the wall increases with increasing pressure drop, independently of RBC concentration, and that the tendency for FNP margination decreases with increasing hematocrit. This work highlights the importance of taking into account RBC-drug carrier interactions and physiological conditions in microcirculation when planning a drug delivery strategy based on systemically administered carriers.

AB - The last decade has seen the emergence of vascular-targeted drug delivery systems as a promising approach for the treatment of many diseases, such as cardiovascular diseases and cancer. In this field, one of the major challenges is carrier margination propensity (i.e., particle migration from blood flow to vessel walls); indeed, binding of these particles to targeted cells and tissues is only possible if there is direct carrier-wall interaction. Here, a microfluidic system mimicking the hydrodynamic conditions of human microcirculation in vitro is used to investigate the effect of red blood cells (RBCs) on a carrier margination in relation to RBC concentration (hematocrit) and pressure drop. As model drug carriers, fluorescent polymeric nanoparticles (FNPs) were chosen, which were obtained by using as starting material a pegylated polylactic acid-polyaspartamide copolymer. The latter was synthesized by derivatization of,-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) with Rhodamine (RhB), polylactic acid (PLA) and then poly(ethyleneglycol) (PEG) chains. It was found that the carrier concentration near the wall increases with increasing pressure drop, independently of RBC concentration, and that the tendency for FNP margination decreases with increasing hematocrit. This work highlights the importance of taking into account RBC-drug carrier interactions and physiological conditions in microcirculation when planning a drug delivery strategy based on systemically administered carriers.

KW - Margination; Poly(ethylene glycol) (PEG); Poly(lactic acid) (PLA); Polymeric nanoparticles; alpha,beta-poly-(N-2-hydroxyethyl)-DL-aspartamide (PHEA);

UR - http://hdl.handle.net/10447/248400

UR - http://www.mdpi.com/1420-3049/22/11/1845/pdf

M3 - Article

VL - 22

SP - 1845-

JO - Molecules

JF - Molecules

SN - 1420-3049

ER -